An acute myocardial infarction, particularly one that is large and transmural, can produce alterations in the topography of both the infarcted and noninfarcted regions of the ventricle. This remodeling can importantly affect the function of the ventricle and the prognosis for survival. In the early period, infarct expansion has been recognized by echocardiography as a lengthening of the noncontractile region. The noninfarcted region also undergoes an important lengthening that is consistent with a secondary volume-overload hypertrophy and that can be progressive. The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival. The process of ventricular enlargement can be influenced by three interdependent factors, that is, infarct size, infarct healing, and ventricular wall stresses. A most effective way to prevent or minimize the increase in ventricular size after infarction and the consequent adverse effect on prognosis is to limit the initial insult. Acute reperfusion therapy has been consistently shown to result in a reduction in ventricular volume. The reestablishment of blood flow to the infarcted region, even beyond the time frame for myocyte salvage, has beneficial effects in attenuating ventricular enlargement. The process of scarification can be interfered with during the acute infarct period by the administration of glucocorticosteroids and nonsteroidal antiinflammatory agents, which result in thinner infarcts and greater degrees of infarct expansion. Modification of distending or deforming forces can importantly influence ventricular enlargement. Even short-term augmentations in afterload have deleterious long-term effects on ventricular topography. Conversely, judicious use of nitroglycerin seems to be associated with an attenuation of infarct expansion and long-term improvement in clinical outcome. Long-term therapy with an angiotensin converting enzyme inhibitor can favorably alter the loading conditions on the left ventricle and reduce progressive ventricular enlargement as demonstrated in both experimental and clinical studies. With the former therapy, this attenuation of ventricular enlargement was associated with a prolongation in survival. The long-term clinical consequences of long-term angiotensin converting enzyme inhibitor therapy after myocardial infarction is currently being evaluated. Although studies directed at attenuating left ventricular remodeling after infarction are in the early stages, it does seem that this will be an important area in which future research might improve long-term outcome after infarction.

Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications.

Left ventricular remodeling is the process by which ventricular size, shape, and function are regulated by mechanical, neurohormonal, and genetic factors.1 2 Remodeling may be physiological and adaptive during normal growth or pathological due to myocardial infarction, cardiomyopathy, hypertension, or valvular heart disease (Figure 1⇓). This article will review postinfarction remodeling, pathophysiological mechanisms, and therapeutic intervention.



 Figure 1. 
Diagrammatic representation of the many factors involved in the pathophysiology of ventricular remodeling. ECM indicates extracellular matrix; RAAS, renin-angiotensin-aldosterone system; CO, cardiac output; SVR, systemic vascular resistance; LV, left ventricular; and AII, angiotensin II.



### Postinfarction Left Ventricular Remodeling

The acute loss of myocardium results in an abrupt increase in loading conditions that induces a unique pattern of remodeling involving the infarcted border zone and remote noninfarcted myocardium. Myocyte necrosis and the resultant increase in load trigger a cascade of biochemical intracellular signaling processes that initiates and subsequently modulates reparative changes, which include dilatation, hypertrophy, and the formation of a discrete collagen scar. Ventricular remodeling may continue for weeks or months until the distending forces are counterbalanced by the tensile strength of the collagen scar. This balance is determined by the size, location, and transmurality of the infarct, the extent of myocardial stunning, the patency of the infarct-related artery, and local tropic factors.1 3 

The myocardium consists of 3 integrated components: myocytes, extracellular matrix, and the capillary microcirculation that services the contractile unit assembly. Consideration of all 3 components provides important insights into the remodeling process and a rationale for future therapeutic strategies. The cardiomyocyte is terminally differentiated and develops tension by shortening. The extracellular matrix provides a stress-tolerant, viscoelastic scaffold consisting of type I and type III collagen that couples myocytes and maintains the spatial relations between the myofilaments and their capillary microcirculation.4 5 The collagen framework couples adjacent myocytes by intercellular struts that …

Left Ventricular Remodeling After Myocardial Infarction Pathophysiology and Therapy

Background—The extent of microvascular obstruction during acute coronary occlusion may determine the eventual magnitude of myocardial damage and thus, patient prognosis after infarction. By contras...

Prognostic Significance of Microvascular Obstruction by Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673696025147.pdf

Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour.

Background Despite remarkable advances in the treatment of acute myocardial infarction, substantial early patient mortality remains. Appropriate choices among alternative therapies and the use of clinical resources depend on an estimate of the patient's risk. Individual patients reflect a combination of clinical features that influence prognosis, and these factors must be appropriately weighted to produce an accurate assessment of risk. Prior studies to define prognosis either were performed before widespread use of thrombolysis or were limited in sample size or spectrum of data. Using the large population of the GUSTO-I trial, we performed a comprehensive analysis of relations between baseline clinical data and 30-day mortality and developed a multivariable statistical model for risk assessment in candidates for thrombolytic therapy. Methods and Results For the 41 021 patients enrolled in GUSTO-I, a randomized trial of four thrombolytic strategies, relations between clinical descriptors routinely collected at initial presentation, and death within 30 days (which occurred in 7% of the population) were examined with both univariable and multivariable analyses. Variables studied included demographics, history and risk factors, presenting characteristics, and treatment assignment. Risk modeling was performed with logistic multiple regression and validated with bootstrapping techniques. Multivariable analysis identified age as the most significant factor influencing 30-day mortality, with rates of 1.1% in the youngest decile ( 75 (adjusted chi(2)=717, P<.0001). Other factors most significantly associated with increased mortality were lower systolic blood pressure (chi(2)=550, P<.0001), higher Killip class (chi(2)=350, P<.0001), elevated heart rate (chi(2)=275, P<.0001), and anterior infarction (chi(2)=143, P<.0001). Together, these five characteristics contained 90% of the prognostic information in the baseline clinical data. Other significant though less important factors included previous myocardial infarction, height, time to treatment, diabetes, weight, smoking status, type of thrombolytic, previous bypass surgery, hypertension, and prior cerebrovascular disease. Combining prognostic variables through logistic regression, we produced a validated model that stratified patient risk and accurately estimated the likelihood of death. Conclusions The clinical determinants of mortality in patients treated with thrombolytic therapy within 6 hours of symptom onset are multifactorial and the relations complex. Although a few variables contain most of the prognostic information, many others contribute additional independent prognostic information. Through consideration of multiple characteristics, including age, medical history, physiological significance of the infarction, and medical treatment, the prognosis of an individual patient can be accurately estimated.

/pdf/predictors-of-30-day-mortality-in-the-era-of-reperfusion-for-27yvi1iwib.pdf

Predictors of 30-Day Mortality in the Era of Reperfusion for Acute Myocardial Infarction Results From an International Trial of 41 021 Patients

In a double-blind trial of streptokinase for acute myocardial infarction, 219 consecutive patients presenting with infarction within four hours (mean, 3.0 +/- 0.8) of the onset of chest pain were randomly assigned to treatment with streptokinase (1.5 million units) or placebo, given intravenously over 30 minutes. The primary end point of the study was left ventricular function in patients with first infarctions. Patients who could undergo beta-blockade also received intravenous propranolol. Heparin (for 48 hours) and a combination of low-dose aspirin and dipyridamole were administered to both groups until cineangiography was performed at three weeks. In the patients with first infarctions treated with streptokinase, the left ventricular ejection fraction was 6 percentage points higher (streptokinase vs. placebo, 59 +/- 10.5 vs. 53 +/- 13.5 percent; P less than 0.005), with benefit to patients with either anterior infarction (57 +/- 11.9 vs. 49 +/- 15.9 percent; P less than 0.05) or inferior infarction (60 +/- 9.1 vs. 55 +/- 11.3 percent; P less than 0.05). Left ventricular function was improved regardless of whether concomitant propranolol was given. Survival (at 30 days) was improved with streptokinase: 2 deaths occurred among 79 patients who received this drug, as compared with 12 deaths among 93 patients who received placebo (2.5 vs. 12.9 percent, P = 0.012). Rates of reinfarction (streptokinase vs. placebo, 3 vs. 1 percent) and requirements for surgery or angioplasty (7 vs. 5 percent) were similar in the two groups. We conclude that administration of intravenous streptokinase (1.5 million units) to patients with a first myocardial infarction results in improved left ventricular function and short-term survival.

Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction.

In a double-blind trial comparing two thrombolytic agents as treatment for acute myocardial infarction, we randomized 270 consecutive patients an average (±SD) of 2.5±0.6 hours after the onset of chest pain from a first myocardial infarction — 135 to receive intravenous streptokinase (1.5 million units over 30 minutes) and 135 to receive intravenous recombinant tissue plasminogen activator (rt-PA) (100 mg over three hours). The primary end point was left ventricular function as assessed by cineangiography performed three weeks after infarction. The effects of the two agents on left ventricular function were similar. The ejection fraction was identical (58±12 percent) in both groups. The end-systolic volume was 61 ±29 ml in the streptokinase group and 66±31 ml in the rt-PA group (P not significant). Patency rates at three weeks for the infarct-related artery were also similar (75 percent in the streptokinase group and 76 percent in the rt-PA group). Reinfarction rates at 30 days were the same (5 p...

https://www.nejm.org/doi/pdf/10.1056/NEJM198903303201301?listPDF=true

Effect of intravenous streptokinase as compared with that of tissue plasminogen activator on left ventricular function after first myocardial infarction.

Reinfarction after thrombölytic therapy for acute myocardial infarction followed by conservative management: Incidence and effect of smoking

Regional diastolic wall motion was studied with sonomicrometry in 30 open chest anaesthetised dogs after left anterior descending stenosis or occlusion. Post-systolic shortening and thickening, defined as the magnitude of segment shortening or wall thickening that occurred after end systole, was measured in peripheral and central ischaemic segments. These post-systolic events developed concurrently with impaired systolic shortening or thickening, either immediately after acute coronary occlusion or during progressive stenosis, and persisted with the development of dyskinesis and during reperfusion. The magnitude of these events in dyskinetic segments of 24 dogs was considerable, reaching 50(2)% (mean(SEM)) and 33(3)% of shortening or thickening that was present before coronary occlusion. Post-systolic shortening and thickening were maximum at 100(2) ms after peak negative dP/dt. Significant correlations were found between systolic shortening or thickening before coronary occlusion and post-systolic shortening (r=0.74, 56 segments) or thickening (r=0.84, 19 segments) after occlusion, but there was no correlation between post-systolic shortening or thickening and dyskinetic lengthening or thinning. In seven dogs followed for 4 h after coronary occlusion post-systolic shortening fell by 15% in peripheral segments and by 70% in central segments (p<0.002). In 17 dogs reperfused after 60 (n=9) or 90 (n=8) min of coronary occlusion the maximal recovery of systolic shortening early after reperfusion was significantly related to the magnitude of post-systolic shortening immediately before reperfusion (60 min occlusion r=0.84, 90 min occlusion r=0.88). These data show that post-systolic shortening is a marker of potential for early recovery of function of acutely ischaemic myocardium and suggest that it is due, at least in part, to an active process.

Post-systolic shortening a marker of potential for early recovery of acutely ischaemic myocardium in the dog

Thrombolytic treatment for acute myocardial infarction increases the risk of subsequent reocclusion of the infarct related artery. The efficacy and safety of repeat thrombolytic treatment was assessed in 31 patients treated with streptokinase (n = 13) or tissue plasminogen activator (n = 18) a median of five days (1-716) after the first infusion. The indication for readministration was prolonged chest pain with new ST segment elevation. Efficacy was assessed by infarct artery patency at angiography at a median of eight days after readministration in 22 patients and by non-invasive criteria in 23 patients (reperfusion was deemed to be likely if serum creatine kinase was not increased or reached a peak less than 12 hours after infarction). Angiography showed patency of 70% of the infarct arteries after readministration of streptokinase and of 75% after tissue plasminogen activator. The corresponding patency rates assessed noninvasively were 73% and 75%. Reinfarction was prevented in nine (29%) patients. Allergic reactions occurred in four of eight patients who received streptokinase twice (plasmacytosis and acute reversible renal failure developed in one patient). Two patients had major bleeding and two minor bleeding, all after tissue plasminogen activator, and one of them died of cerebral haemorrhage. Repeat thrombolytic treatment results in late patency rates similar to the rates after the initial administration. Allergic reactions were common in those treated twice with streptokinase.

https://heart.bmj.com/content/heartjnl/64/3/177.full.pdf

Robin M. Norris

Papers

Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction.

Effect of intravenous streptokinase as compared with that of tissue plasminogen activator on left ventricular function after first myocardial infarction.

Reinfarction after thrombölytic therapy for acute myocardial infarction followed by conservative management: Incidence and effect of smoking

Post-systolic shortening a marker of potential for early recovery of acutely ischaemic myocardium in the dog

Safety and efficacy of repeat thrombolytic treatment after acute myocardial infarction.